Different mutation profiles associated to P53 accumulation in colorectal cancer

Abstract

The tumor suppressor TP53 gene is one of the most frequently mutated in different types of human cancer. Particularly in colorectal cancer (CRC), it is believed that TP53 mutations play a role in the adenoma-carcinoma transition of tumors during pathological process. In order to analyze TP53 expressed alleles in CRC, we examined TP53 mRNA in tumor samples from 101 patients with sporadic CRC. Samples were divided in two groups defined according to whether they exhibit positive or negative P53 protein expression as detected by immunohistochemistry (IHC). The presence of TP53 mutation was a common event in tumors with an overall frequency of 54.5%. By direct sequencing, we report 42 different TP53 sequence changes in 55 CRC patients, being two of them validated polymorphisms. TP53 mutations were more frequent in positive than in negative P53 detection group (p<0.0001), being the precise figures 79.6% and 30.8%, respectively. In addition, the mutation profiles were also different between the two groups of samples; while most of the mutations detected in P53 positive group were missense (38 out of 39), changes in P53 negative detection group include 7 insertions/deletions, 6 missense, 2 nonsense and 1 silent mutation. As previously observed, most mutations were concentrated in regions encoding P53 DNA binding domain (DBD). Codons 175, 248 and 273 together account for 36.7% of point mutations, in agreement with previous observations provided that these codons are considered mutation hotspots. Interestingly, we detected two new deletions and two new insertions. In addition, in three samples we detected two deletions and one insertion that could be explained as putative splicing variants or splicing errors.

Detection of miR-34a Promoter Methylation in Combination with Elevated Expression of c-Met and β-Catenin Predicts Distant Metastasis of Colon Cancer

“…Interestingly, neither expression nor methylation of miR-34a was associated with increased p53 protein expression, which is known to correlate with mutations in the p53 gene (ref. 31; data not shown).…”

Correlation and prognostic significance of PD-L1 and P53 expression in resected primary pulmonary lymphoepithelioma-like carcinoma

“…Like with ovarian carcinoma, colorectal cancer, and glioblastoma multiforme, etc. (27)(28)(29)(30), the optimal thresholds of P53 positivity in LELC of the lung is still debated and further research studies are warranted. We calculated different cutoff values in our cohort including 1%, 5%, 10%, and 50%, and found that 10% is the most appropriate one to be of prognostic value.…”

Molecular cloning, expression of a galectin gene in Pacific white shrimp Litopenaeus vannamei and the antibacterial activity of its recombinant protein

“…Galectin promotes survival of naïve hemocytes, but induces apoptosis of activated hemocytes. Activation of hemocyte apoptosis can enhance p53 transcription (Lopez et al, 2012); p53 induces cell cycle arrest and apoptotic cell death. V. alginolyticus challenge of Lvgalectin-silenced shrimp also induced the expression of multiple antimicrobial peptides (LvPEN3 and LvCrustrin), which reportedly increases Lvp53 expression and promotes the expression of LvproPO to reduce ROS levels.…”